The present invention relates to devices, systems, and methods for measuring analytes from biological samples, such as from a sample of bodily fluid. More specifically, the present invention relates to biosensors and methods for testing an analyte using certain electrical response characteristics.
Measuring the concentration of substances, particularly in the presence of other, confounding substances (“interferents”), is important in many fields, and especially in medical diagnosis and disease management. For example, the measurement of glucose in bodily fluids, such as blood, is crucial to the effective treatment of diabetes.
Multiple methods are known for measuring the concentration of analytes such as glucose in a blood sample. Such methods typically fall into one of two categories: optical methods and electrochemical methods. Optical methods generally involve absorbance, reflectance or laser spectroscopy to observe the spectrum shift in the fluid caused by the concentration of the analytes, typically in conjunction with a reagent that produces a known color when combined with the analyte. Electrochemical methods generally rely upon the correlation between a charge-transfer or charge-movement property of the blood sample (e.g., current, interfacial potential, impedance, conductance, and the like) and the concentration of the analyte, typically in conjunction with a reagent that produces or modifies charge-carriers when combined with the analyte. See, for example, U.S. Pat. No. 4,919,770 to Preidel, et al., and U.S. Pat. No. 6,054,039 to Shieh, which are incorporated by reference herein in their entireties.
An important limitation of electrochemical methods of measuring the concentration of a chemical in blood is the effect of confounding variables on the impedance of a blood sample. For example, the geometry of the blood sample must correspond closely to that upon which the impedance-to-concentration mapping function is based.
The geometry of the blood sample is typically controlled by a sample-receiving portion of the testing apparatus. In the case of blood glucose meters, for example, the blood sample is typically placed onto a disposable test strip that plugs into the meter. The test strip may have a sample chamber to define the geometry of the sample. Alternatively, the effects of sample geometry may be limited by assuring an effectively infinite sample size. For example, the electrodes used for measuring the analyte may be spaced closely enough so that a drop of blood on the test strip extends substantially beyond the electrodes in all directions. Regardless of the strategy used to control sample geometry, typically one or more dose sufficiency electrodes are used to assure that there is a sufficient amount of sample to assure an accurate test result.
Other examples of limitations to the accuracy of blood glucose measurements include variations in blood chemistry (other than the analyte of interest being measured). For example, variations in hematocrit (concentration of red blood cells) or in the concentration of other chemicals, constituents or formed elements in the blood, may affect the measurement. Variation in the temperature of blood samples is yet another example of a confounding variable in measuring blood chemistry.
Thus, a system and method are needed that accurately measure blood glucose, even in the presence of confounding variables, including variations in temperature, hematocrit, and the concentrations of other chemicals in the blood. A system and method are likewise needed that accurately measure an analyte in a fluid. It is an object of the present invention to provide such a system and method.
Many approaches have been employed to attenuate or mitigate the influence of one or more sources of interference, or to otherwise compensate for or correct a measured value. Often multiple design solutions are employed to adequately compensate for the sensitivities associated with the chosen measurement method.
Well known design solutions involve perm-selective and/or size-selective membranes, filters or coatings. Such design solutions suffer from incremental costs of goods, additive manufacturing process steps further exacerbating manufacturing cost, complexity, and speed of manufacture. Systems (disposable test strips and instruments) employing these methods take the general approach of overcoming the problem within the scope of the test strip design.
Another general approach involves the use of sophisticated excitation and signal processing methods coupled with co-optimized algorithms. Simpler, less complex, test strip architectures and manufacturing processes may be realized; however, instrumentation costs, memory and processor requirements, associated complex coding, and calibrated manufacturing techniques are required. Systems employing this technique take the general approach of overcoming the problem within the scope of the instrumentation.
A more recent approach involves neither the strip nor instrumentation, per se, but rather exploits the measurement methodology. An example of this is the use of a coulometric method to attenuate the influence of hematocrit and temperature.
It is also well known to those skilled in the art that all of the above approaches are further supported by the initial design of reagent systems. In the detection of glucose, for example, this may involve the use of selective redox mediators and enzymes to overcome the detrimental influence of redox-active species or the presence of other sugars.
It is an object of the invention to provide a simpler, less costly method for attenuating the influence of interferents, in a manner that does not suffer the demerits associated with the general approaches currently in wide use.